This contact was established to evaluate the potential for environmental agents, therapeutic drugs or biological materials to induce immunotoxicity, altered hypersensitivity responses or autoimmune disease in rodent models. This is accomplished via three mechanisms. The first mechanism is to examine the ability of test chemical to modulate immune responses using a defined and validated panel of immune function tests, host resistance models and hypersensitivity assays in rodents. These studies will provide assessment of the potential hazards of human exposure and increase the database regarding the number of chemicals which affect the immune system. A second objective is to develop and validate new methodologies and make use of advancements in the fields of molecular biology and toxicology, to increase the predictive value of the standardized testing panels used to evaluate immunotoxicity. Examples of such new developments include the use of the RNAse protection assay to establish cytokine profiles for chemical irritants and sensitizers. Finally, studies conducted under this contract will address the underlying cellular and molecular basis for observed alterations in immune functions. Molecular techniques such as RT-PCR, analysis of cell activation markers and evaluation of targeted cell subpopulations will help elucidate the specific cellular targets of immunotoxic agents and suggest potential strategies for minimizing risks to the human population.